Abstract
Background:
Lipid peroxidation mediated by reactive oxygen species is a major contributor to oxidative stress. Docosahexaenoic acid (DHA) has anti-oxidant and neuroprotective properties. Our objective was to assess how oxidative stress measured by lipid peroxidation was modified by DHA in a newborn piglet model of hypoxia-ischemia (HI).
Methods:
Fifty-five piglets were randomized to (i) hypoxia, (ii) DHA, (iii) hypothermia, (iv) hypothermia+DHA or (v) sham. All groups but sham were subjected to hypoxia by breathing 8% O2. DHA was administered 210 min after end of hypoxia and the piglets were euthanized 9.5 h after end of hypoxia. Urine and blood were harvested at these two time points and analyzed for F4-neuroprostanes, F2-isoprostanes, neurofuranes and isofuranes using UPLC-MS/MS.
Results:
F4-neuroprostanes in urine were significantly reduced (P=0.006) in groups receiving DHA. Hypoxia (median, IQR 1652 nM, 610–4557) vs. DHA (440 nM, 367–738, P=0.016) and hypothermia (median, IQR 1338 nM, 744–3085) vs. hypothermia+DHA (356 nM, 264–1180, P=0.006). The isoprostane compound 8-iso-PGF2α was significantly lower (P=0.011) in the DHA group compared to the hypoxia group. No significant differences were found between the groups in blood.
Conclusion:
DHA significantly reduces oxidative stress by measures of lipid peroxidation following HI in both normothermic and hypothermic piglets.
Author statement
Conflict of interest: Authors state no conflict of interest.
Material and Methods: Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
Financial support: South-Eastern Norway Regional Health Authority, Hamar, Norway; Norwegian SIDS and Stillbirth Society, Oslo, Norway; Laerdal Foundation, Stavanger, Norway and Renée and Bredo Grimsgaard’s foundation, Oslo, Norway.
For analysis carried out in Valencia, Spain, these were supported by PI14/0443 grant from the Instituto de Investigación Sanitaria Carlos III to MV, MCC and JE.
Disclosure: We have nothing to disclose and no conflict of interest.
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